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Prospective Study of VEGFR-2 /IL-8 Genetic Interaction in MBC Treated With Paclitaxel and Bevacizumab vs. Chemotherapy (BEVAPROS)

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ClinicalTrials.gov Identifier: NCT02329639
Recruitment Status : Recruiting
First Posted : December 31, 2014
Last Update Posted : October 25, 2017
Sponsor:
Information provided by (Responsible Party):
Guido Bocci, University of Pisa

Brief Summary:
Metastatic Breast cancer (MBC) patients from ten Italian Divisions of Medical Oncology, with histologically confirmed HER2-negative MBC, treated with a first-line therapy including bevacizumab 10 mg/m2 i.v. on days 1 and 15 combined with first-line paclitaxel 90 mg/m2 i.v. on days 1,8 and 15, every 4 weeks, will be enrolled for the present pharmacogenetic study. MBC patients treated with first-line chemotherapy including paclitaxel without bevacizumab will be also enrolled as control group.

Condition or disease Intervention/treatment
Metastatic Breast Cancer Genetic: genetic interaction analysis

Detailed Description:
Metastatic Breast Cancer (MBC) patients from ten Italian Divisions of Medical Oncology, with histologically confirmed HER2-negative MBC, treated with a first-line therapy including bevacizumab 10 mg/m2 i.v. on days 1 and 15 combined with first-line paclitaxel 90 mg/m2 i.v. on days 1,8 and 15, every 4 weeks, will be enrolled for the present pharmacogenetic study. MBC patients treated with a first-line chemotherapy without bevacizumab will be also enrolled as control group. Sites of metastatic disease will be radiologically re-evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1, in patients with measurable disease. In patients without measurables lesions, progression of disease will be defined when new lesions appeared or when existing lesions evolved. In the case of non measurables lesions, deterioration of clinical condition not due to treatment toxicity, will be defined as progression disease. Progression-free survival (PFS), will be defined as the period of time from the beginning of the treatment to the first observation of disease progression as above described, or death from any cause. All patients will be for response, PFS and overall survival. Each patient entering the study will sign the informed consent. The protocol has been approved by Ethics Committee Vast Area Northwest of Tuscany (CEAVNO), Pisa, Italy (30/04/2014). Genotyping analyses blood samples (3 ml.) will be collected in ethylenediaminetetraacetic acid tubes and stored at -80° C. Genes and polymorphisms involved in the angiogenesis pathway and already suggested as predictors of bevacizumab response, will be chosen for the present analyses. Germline DNA extraction will be performed using QIamp DNA Blood Mini Kit (Qiagen, Valencia, California, USA). Allelic discrimination of genes will be performed using an ABI PRISM 7900 SDS Instrument (Applied Biosystems, Carlsbad, California, USA) and with validated TaqMan single nucleotide polymorphism (SNP) genotyping assays (Applied Byosistems). Polymerase chain reactions will be carried out according to the manufacturer's protocol. Genotyping will be not performed until an adequate number of events (>80% on study population) will be reported in terms of PFS. Statistical analysis: The first aim of this prospective analysis will be evaluate the possible role of VEGFR-2 rs11133360/IL-8 rs4073 polymorphism genetic interaction to predict the bevacizumab response in terms of PFS. The secondary end-points will be the correlations with overall survival (OS) and response rate. All polymorphisms will be analyzed for deviation from the Hardy-Weinberg Equilibrium (HWE) by means of comparison between observed allelic distributions with those expected from the HWE by on x2 test. Any correlation between gene polymorphisms and response rate will be analyzed by the two-sided Fisher's Exact Test. The association between each individual polymorphism and the most relevant clinical-pathological characteristics with PFS will be tested using a Cox proportional hazards model. The Multifactor Dimensionality Reduction (MDR) methodology will be applied (using version 2.0 beta 6 of MDR software available on http://sourceforge.net/projects/mdr/) to investigate the role of an interaction between gene polymorphisms in identifying biomarkers of paclitaxel plus bevacizumab response. The genotype combination with the highest PFS benefit correlated with an OS improvement will be chosen for further analyses. The difference in PFS between favourable genetic profiles and the unfavourable genetic profiles will be assessed with the log-rank test and the kaplan-Meier method to evaluate survival curves. A Cox proportional hazards model, with the possible genetic profiles and the clinical and pathological patient characteristics individually correlated with the PFS, will be used to calculate the adjusted hazards ratio (HR) and the 95% confidence interval (95% CI). A P value of<0.05 will be accepted as statistically significant. Tha Kaplan-Meier and Cox proportional hazards analyses will be performed using the SPSS version 17.0 (SPSS, Chicago, IL).

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Study Type : Observational
Estimated Enrollment : 189 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective Evaluation of VEGFR-2 rs11133360/IL-8 rs4073 Genetic Interaction in Metastatic Breast Cancer Patients Treated With Paclitaxel and Bevacizumab vs. Chemotherapy Alone (BEVAPROS)
Study Start Date : April 2014
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
case group
genetic interaction analysis of women with HER2 negative metastatic breast cancer performing a first-line chemotherapy with bevacizumab
Genetic: genetic interaction analysis
VEGFR-2 rs11133360/IL-8 rs4073 genetic interaction analysis

control group
genetic interaction analysis of women with HER2 negative metastatic breast cancer performing a first-line chemotherapy without bevacizumab
Genetic: genetic interaction analysis
VEGFR-2 rs11133360/IL-8 rs4073 genetic interaction analysis




Primary Outcome Measures :
  1. Progression free survival [ Time Frame: 24 months ]
    progression free survival in an unselected population of metastatic breast cancer patients treated with first-line paclitaxel and bevacizumab or with chemotherapy alone, assessed through the multifactor dimensionality reduction methodology (genetic interaction analysis)


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 24 months ]
    overall survival in an unselected population of metastatic breast cancer patients treated with first-line paclitaxel and bevacizumab or with chemotherapy alone, assessed through the multifactor dimensionality reduction methodology (genetic interaction analysis)


Biospecimen Retention:   Samples With DNA
whole blood


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
MBC patients treated with a first-line chemotherapy including paclitaxel with or without bevacizumab
Criteria

Inclusion Criteria:

  • histologically confirmed HER2-negative MBC, treated with a first-line therapy including bevacizumab 10 mg/m2 i.v. on days 1 and 15 combined with first-line paclitaxel 90 mg/m2 i.v. on days 1,8 and 15,every 4 weeks, will be enrolled for the present pharmacogenetic study. MBC patients treated with a first-line chemotherapy without bevacizumab will also be enrolled as control goup.

Exclusion Criteria:

  • histologically not confirmed HER2-negative MBC, and patients not treated with a first-line chemotherapy with or without bevacizumab.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02329639


Contacts
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Contact: Giacomo Allegrini, MD +39-0587-273104 g.allegrini@usl5.toscana.it
Contact: Guido Bocci, MD, PhD +39-050-2218756 guido.bocci@med.unipi.it

Locations
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Italy
Department of Clinical and Experimental Medicine, University of Pisa Recruiting
Pisa, I am not in the U.S. or Canada, Italy, 56125
Contact: Guido Bocci, MD, PhD    +390502218756    guido.bocci@med.unipi.it   
Contact: Giacomo Allegrini, MD    +390587273104    g.allegrini@usl5.toscana.it   
Principal Investigator: Guido Bocci, MD, PhD         
Azienda USL 5 of Pisa Recruiting
Pontedera, Pisa, Italy, 56025
Contact: Giacomo Allegrini, MD    +39-0587-273104    g.allegrini@usl5.toscana.it   
Contact: Guido Bocci, MD, PhD    +39-050-2218756    guido.bocci@med.unipi.it   
Sponsors and Collaborators
University of Pisa
Investigators
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Principal Investigator: Guido Bocci, MD, PhD Dept. of Clinical and Experimental Medicine, University of Pisa

Publications:
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Responsible Party: Guido Bocci, MD,PhD, University of Pisa
ClinicalTrials.gov Identifier: NCT02329639     History of Changes
Other Study ID Numbers: University of Pisa - Az. USL 5
First Posted: December 31, 2014    Key Record Dates
Last Update Posted: October 25, 2017
Last Verified: October 2017

Keywords provided by Guido Bocci, University of Pisa:
bevacizumab
paclitaxel
pharmacogenetics
breast cancer

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Bevacizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors